Rapid discontinuation of prednisone in kidney transplant recipients from at‐risk subgroups: an OPTN/SRTR analysis

Abstract

Summary Although rapid discontinuation of prednisone (RDP) after kidney transplantation has been successful in low‐risk recipients, there is concern about RDP use in recipients at increased risk for rejection or recurrent disease. Using SRTR, we compared outcomes for RDP versus maintenance prednisone‐treated recipients for all adult 1st and 2nd transplants (n = 169 479) and the following 1st transplant subgroups: African American (AA); highly sensitized; those with a potentially recurrent disease; and pediatric recipients. For all adult 1st LD and DD transplants, RDP was associated with better patient and graft survival. For all LD subgroups, RDP and maintenance prednisone were associated with similar patient, graft, and death‐censored (DC) graft survival. For 1st transplant DD subgroups, RDP was associated with better patient survival in AA, those with potentially recurrent disease, and pediatric recipients; graft survival with RDP was better in AAs. For adult 2nd DD transplants, RDP was associated with worse DC‐graft survival. Importantly, for all differences, the effect size was small. With the exception of 2nd DD transplants, RDP protocols can be used without decreasing patient or graft survival for subgroups of 1st DD and LD kidney transplant recipients and for 2nd LD transplant recipients, at increased risk of rejection or recurrent disease.

Current Status of Glucocorticoid Usage in Solid Organ Transplantation

“…Although, firstly steroid sparing immunosuppressive regimens were used for low immunologic risk patients, an analysis of 169479 renal transplant patients using SRTR exhibited that rapid discontinuation of steroids can be used in all adult and pediatric first kidney transplant recipients from deceased or living donor and even in second kidney transplant recipients from living donor or patients at risk for rejection or recurrence of underlying diseases, without decreasing patients' or graft survivals. Only in adult patients with second kidney transplantation from deceased donor, rapid steroid withdrawal was associated with worse graft survival [9] . Another systematic review and meta-analysis consisting 7 cohort studies that included even high-risk kidney transplant patients such as re-transplant patients, African-American ethnicity or recipients with panel reactive antibody (PRA) of 20% or more found that acute rejection episodes and graft loss were comparable between patients maintained on steroids compared with steroid withdrawal or avoidance group.…”

“…As maintenance immunosuppressive therapy, some centers are shifting toward steroid sparing maintenance immunosuppressive regimens by different steroid withdrawal or avoidance protocols [1][2][3] . Steroid sparing means rapid, early, or late steroid discontinuation (within one week to several months after transplantation), while steroid avoidance refers to avoiding steroid use in regimens with or without initial high corticosteroid induction therapy [3,[9][10][11][12] . Although old studies on steroid sparing regimens that usually were GC minimization or discontinuation after 3 months of transplant surgery showed higher rates of acute rejection and graft loss, in those studies immunosuppressive regimens contained cyclosporine as a CNI [13] .…”

Current status of glucocorticoid usage in solid organ transplantation

“…As maintenance immunosuppressive therapy, some centers are shifting toward steroid sparing maintenance immunosuppressive regimens by different steroid withdrawal or avoidance protocols[ 1 - 3 ]. Steroid sparing means rapid, early, or late steroid discontinuation (within 1 wk to several months after transplantation), while steroid avoidance refers to avoiding steroid use in regimens with or without initial high corticosteroid induction therapy[ 3 , 9 - 12 ]. Although old studies on steroid sparing regimens (GC minimization or discontinuation after 3 mo of transplant surgery) showed higher rates of acute rejection and graft loss, in those studies immunosuppressive regimens contained cyclosporine as a CNI[ 13 ].…”

“…Although old studies on steroid sparing regimens (GC minimization or discontinuation after 3 mo of transplant surgery) showed higher rates of acute rejection and graft loss, in those studies immunosuppressive regimens contained cyclosporine as a CNI[ 13 ]. Nowadays, induction therapies with thymoglobulin or IL2 receptor antagonists and new maintenance immunosuppressive regimens, such as tacrolimus instead of cyclosporine as CNI or mTOR inhibitors, in combination with low doses of CNIs and/or mycophenolate, provided the opportunity for successful steroid-sparing immunosuppression regimens[ 1 , 9 - 11 , 14 , 15 ]. Although, steroid sparing immunosuppressive regimens were used for low immunological risk patients, an analysis of 169479 renal transplant patients using the Scientific Registry of Transplant Recipients found that rapid discontinuation of steroids can be used in all adult and pediatric first kidney transplant recipients from either a deceased or living donor and in second kidney transplant recipients from a living donor or patients at risk for rejection or recurrence of underlying diseases without decreasing patients’ or graft survival rates.…”

“…Although, steroid sparing immunosuppressive regimens were used for low immunological risk patients, an analysis of 169479 renal transplant patients using the Scientific Registry of Transplant Recipients found that rapid discontinuation of steroids can be used in all adult and pediatric first kidney transplant recipients from either a deceased or living donor and in second kidney transplant recipients from a living donor or patients at risk for rejection or recurrence of underlying diseases without decreasing patients’ or graft survival rates. Rapid steroid withdrawal was only associated with worse graft survival[ 9 ] in adult patients after a second kidney transplantation from a deceased donor. Another systematic review and meta-analysis consisting of seven cohort studies that included high-risk kidney transplant patients, such as re-transplanted patients, African-American ethnicity, or recipients with panel reactive antibody (referred to as PRA) of 20% or more, found that acute rejection episodes and graft loss were comparable between patients maintained on steroids compared with steroid withdrawal or avoidance group.…”